1,2-Dichloroethane → HCID 178482375, compound

HRID 491647Notes

Reaction equation

HRID 491647 reaction equation
[CH3:1][NH:2][C:3]1[N:8]=[C:7]([O:9][C:10]2[CH:11]=[C:12]([NH2:17])[C:13]([NH2:16])=[CH:14][CH:15]=2)[CH:6]=[CH:5][N:4]=1.[Cl:18][C:19]1[CH:32]=[CH:31][C:30]([N:33]=[C:34]=S)=[CH:29][C:20]=1[CH2:21][N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1.C(Cl)CCl>CC#N>[Cl:18][C:19]1[CH:32]=[CH:31][C:30]([NH:33][C:34]2[NH:16][C:13]3[CH:14]=[CH:15][C:10]([O:9][C:7]4[CH:6]=[CH:5][N:4]=[C:3]([NH:2][CH3:1])[N:8]=4)=[CH:11][C:12]=3[N:17]=2)=[CH:29][C:20]=1[CH2:21][N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 177554024-(2-Methylamino-pyrimidin-4-yloxy)-benzene-1,2-diamineHCID 177558431-(2-Chloro-5-isothiocyanato-benzyl)-4-methyl-piperazine

Product 1

HCID 178482375HCID 178482375, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 4-(2-methylamino-pyrimidin-4-yloxy)-benzene-1,2-diamine (Step C, 300 mg, 1.3 mmol, 1.0 eq) in anhydrous CH3CN (20 mL) was added drop-wise a solution of 1-(2-chloro-5-isothiocyanato-benzyl)-4-methyl-piperazine (405 mg [residual imidazole present], 1.3 mmol, 1.0 eq) in anhydrous CH3CN (10 mL). The solution was stirred for 16 h at RT. EDC (250 mg, 1.3 mmol, 1.0 eq) was added and the reaction was heated to 80° C. and stirred for 2 h. The solvent was removed under reduced pressure and residue was dissolved in CH2Cl2/MeOH (50 mL). The organic solution was washed with H2O (25 mL), NaHCO3 (aq, 25 mL) and brine (25 mL). The aqueous layers were back extracted with CH2Cl2 and the combined organic layers were dried over MgSO4, filtered and concentrated. The crude was further purified by column chromatography (0-10% MeOH/CH2Cl2 with 1% NH4OH) followed by preparative TLC and finally reverse phase HPLC (5-100% H2O/CH3CN with 0.1% TFA) to yield [4-chloro-3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-[5-(2-methylamino-pyrimidin-4-yloxy)-1H-benzimidazol-2-yl]-amine. MS m/z=479.2 (M+H)+; MW Calc'd for C24H27ClN8O: 478.20.

Workup

  1. temperaturethe reaction was heated to 80° C.
  2. stirringstirred for 2 h
  3. customThe solvent was removed under reduced pressure and residue
  4. dissolutionwas dissolved in CH2Cl2/MeOH (50 mL)
  5. washThe organic solution was washed with H2O (25 mL), NaHCO3 (aq, 25 mL) and brine (25 mL)
  6. extractionThe aqueous layers were back extracted with CH2Cl2
  7. dry with materialthe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude was further purified by column chromatography (0-10% MeOH/CH2Cl2 with 1% NH4OH)

Sources & evidence

ORD record
ord-da9d2d1b89d24956935dc2b15eac7c4b
Source dataset
uspto-grants-2009_05
Patent number
US07531553B2

Reaction notes

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